Monoclonal Antibody Therapy

 

Monoclonal Antibody Therapy is a form of Immunotherapy that uses monoclonal antibodies (mAb) to bind mono-specifically to certain cells or proteins. This may then stimulate the patient’s immune system to attack those cells.

Monoclonal Antibodies are laboratory-produced versions of immune system proteins that have been engineered to serve as substitute antibodies that can restore, enhance or mimic the immune system’s attack on cancer cells.

Antibodies can be very useful in treating cancer because they can be designed to attack a very specific part of a cancer cell. Monoclonal antibody drugs enlist natural immune system functions to fight cancer. These drugs may be used in combination with other cancer treatments.

 

How does the Immune System Fight Cancer?

The immune system is composed of a complex team of players that detect and destroy disease-causing agents, such as bacteria and viruses. Similarly, this system may eliminate damaged or abnormal cells, such as cancer cells.

One factor in the immune system is the work of antibodies. An antibody attaches itself to a specific molecule (antigen) on the surface of a problematic cell. When an antibody binds to the antigen, it serves as a flag to attract disease-fighting molecules or as a trigger that promotes cell destruction by other immune system processes.

Cancer cells may outpace the immune system, avoid detection, or block immune system activity.

 

How Monoclonal Antibody Drugs Work

Monoclonal antibodies are designed to function in different ways. A particular drug may actually function by more than one means. The role of the drug in helping the immune system may include the following:

  • Flagging Cancer Cells: Some immune system cells depend on antibodies to locate the target of an attack. Cancer cells that are coated in monoclonal antibodies may be more easily detected and targeted for destruction.
  • Triggering Cell-Membrane Destruction: Some monoclonal antibodies can trigger an immune system response that can destroy the outer wall (membrane) of a cancer cell.
  • Blocking Cell Growth: Some monoclonal antibodies block the connection between a cancer cell and proteins that promote cell growth — an activity that is necessary for tumour growth and survival.
  • Preventing Blood Vessel Growth: In order for a cancerous tumour to grow and survive, it needs a blood supply. Some monoclonal antibody drugs block protein-cell interactions necessary for the development of new blood vessels.
  • Blocking Immune System Inhibitors: Certain proteins that bind to immune system cells are regulators that prevent over-activity of the system. Monoclonal antibodies that bind to these immune system cells give the cancer-fighting cells an opportunity to work with less inhibition.
  • Directly Attacking Cancer Cells: Certain monoclonal antibodies may attack the cell more directly, even though they were designed for another purpose. When some of these antibodies attach to a cell, a series of events inside the cell may cause it to self-destruct.
  • Delivering Radiation Treatment: Because of a monoclonal antibody’s ability to connect with a cancer cell, the antibody can be engineered as a delivery vehicle for other treatments. When a monoclonal antibody is attached to a small radioactive particle, it transports the radiation treatment directly to cancer cells and may minimize the effect of radiation on healthy cells. This variation of standard radiation therapy for cancer is called radio immunotherapy.
  • Delivering Chemotherapy: Similarly, some monoclonal antibodies are attached to a chemotherapeutic drug in order to deliver the treatment directly to the cancer cells while avoiding healthy cells.
  • Binding Cancer and Immune Cells: Some drugs combine two monoclonal antibodies, one that attaches to a cancer cell and one that attaches to a specific immune system cell. This connection may promote immune system attacks on the cancer cells.

 

Cancers That Can Be Treated With Monoclonal Antibody Drugs

Monoclonal antibody treatments have been developed for some but not all cancers, and certain types of cancer cells are more vulnerable than others to monoclonal antibody interventions. Nonetheless, treatments have been approved for a number of cancers, including the following:

  • Brain Cancer
  • Breast Cancer
  • Chronic Lymphocytic Leukaemia
  • Colorectal Cancer
  • Head and Neck Cancers
  • Hodgkin’s Lymphoma
  • Lung Cancer
  • Melanoma
  • Non-Hodgkin’s Lymphoma
  • Prostate Cancer
  • Stomach Cancer

 

How Monoclonal Antibody Drugs Are Used In Cancer Treatment

Monoclonal antibodies are administered through a vein (intravenously). How often the monoclonal antibody treatment is administered depends on the cancer and the drug being given. Some monoclonal antibody drugs may be used in combination with other treatments, such as Chemotherapy or Hormone Therapy.

To make a monoclonal antibody, researchers first have to identify the right antigen to attack. For cancer, this is not always easy, and so far mAbs have proven to be more useful against some cancers than others.

Over the past couple of decades, the US Food and Drug Administration (FDA) has approved more than a dozen mAbs to treat certain cancers. As researchers have found more antigens linked to cancer, they have been able to make mAbs against more and more cancers. Clinical trials of newer mAbs are being done on many types of cancer.

Some monoclonal antibody drugs are a part of standard treatment plans. Others are still experimental and used only when all other treatments have been unsuccessful.

 

 

Types of Monoclonal Antibodies

Different types of monoclonal antibodies are used in cancer treatment.

 

Naked Monoclonal Antibodies

Naked mAbs are antibodies that work by themselves. There is no drug or radioactive material attached to them. These are the most common type of mAbs used to treat cancer.

Most naked mAbs attach to antigens on cancer cells, but some work by binding to antigens on other, non-cancerous cells, or even free-floating proteins.

Naked mAbs can work in different ways.

  • Some boost a person’s immune response against cancer cells by attaching to them and acting as a marker for the body’s immune system to destroy them. An example is alemtuzumab (Campath®), which is used to treat some patients with Chronic Lymphocytic Leukaemia (CLL). Alemtuzumab binds to the CD52 antigen, which is found on cells called lymphocytes (which include the leukaemia cells). Once attached, the antibody attracts immune cells to destroy these cells.
  • Some naked mAbs boost the immune response by targeting immune system checkpoints.
  • Other naked mAbs work mainly by attaching to and blocking antigens on cancer cells (or other nearby cells) that help cancer cells grow or spread. For example, trastuzumab (Herceptin®) is an antibody against the HER2 protein. Breast and stomach cancer cells sometimes have large amounts of this protein on their surface. When HER2 is activated, it helps these cells grow. Trastuzumab binds to these proteins and stops them from becoming active.

 

Conjugated Monoclonal Antibodies

Monoclonal antibodies (mAbs) joined to a chemotherapy drug or to a radioactive particle are called conjugated monoclonal antibodies. The mAb is used as a homing device to take one of these substances directly to the cancer cells. The mAb circulates throughout the body until it can find and hook onto the target antigen. It then delivers the toxic substance where it is needed most. This lessens the damage to normal cells in other parts of the body.

Conjugated mAbs are also sometimes referred to as taggedlabeled, or loaded antibodies.

Radiolabeled Antibodies: Radiolabeled antibodies have small radioactive particles attached to them. Ibritumomab tiuxetan (Zevalin®) is an example of a radiolabeled mAb. This is an antibody against the CD20 antigen, which is found on lymphocytes called B cells. The antibody delivers radioactivity directly to cancerous B cells and can be used to treat some types of Non-Hodgkin Lymphoma.

Treatment with this type of antibody is sometimes known as radioimmunotherapy (RIT).

Chemolabeled antibodies: These mAbs have powerful chemotherapy (or other) drugs attached to them. They are also known as antibody-drug conjugates (ADCs). (The drug is often too powerful to be used on its own – it would cause too many side effects if not attached to an antibody.)

Chemolabeled antibodies used to treat cancer include:

  • Brentuximab vedotin (Adcetris®), an antibody that targets the CD30 antigen (found on lymphocytes), attached to a chemo drug called MMAE. This drug is used to treat Hodgkin lymphoma and anaplastic large cell lymphoma.
  • Ado-trastuzumab emtansine (Kadcyla®, also called TDM-1), an antibody that targets the HER2 protein, attached to a chemo drug called DM1. It’s used to treat some breast cancer patients whose cancer cells have too much HER2.

A related drug known as denileukin diftitox (Ontak®) is an immune system protein known as interleukin-2 (IL-2) attached to a toxin from the germ that causes diphtheria. Although it’s not an antibody, IL-2 normally attaches to certain cells in the body that contain the CD25 antigen, which makes it useful for delivering the toxin to these cells. Denileukin diftitox is used to treat lymphoma of the skin (also known as cutaneous T-cell lymphoma). It’s also being studied for use against a number of other cancers.

 

Bispecific Monoclonal Antibodies

These drugs are made up of parts of 2 different mAbs, meaning they can attach to 2 different proteins at the same time. An example is blinatumomab (Blincyto), which is used to treat some types of acute lymphocytic leukemia (ALL).

One part of blinatumomab attaches to the CD19 protein, which is found on some leukemia and lymphoma cells. Another part attaches to CD3, a protein found on immune cells called T cells. By binding to both of these proteins, this drug brings the cancer cells and immune cells together, which is thought to cause the immune system to attack the cancer cells.

 

Side Effects Monoclonal Antibody Drugs Can Cause

In general, monoclonal antibody treatment carries fewer side effects than do traditional chemotherapy treatments.

However, monoclonal antibody treatment for cancer may cause side effects, some of which, though rare, can be very serious. Talk to your doctor about what side effects are associated with the particular drug you’re receiving.

 

Common Side Effects

In general, the more common side effects caused by monoclonal antibody drugs include:

  • Allergic reactions, such as hives or itching
  • Flu-like signs and symptoms, including chills, fatigue, fever, and muscle aches and pains
  • Nausea, vomiting
  • Diarrhoea
  • Skin rashes
  • Low blood pressure

 

Serious Side Effects

Serious, but rare, side effects of monoclonal antibody therapy may include:

  • Infusion Reactions: Severe allergy-like reactions can occur and, in very few cases, lead to death. You may receive medicine to block an allergic reaction before you begin monoclonal antibody treatment. Infusion reactions usually occur while treatment is being administered or soon after, so your health care team will watch you closely for a reaction.
  • Low Blood Cell Counts: Monoclonal antibodies that deliver radioactive particles or chemotherapy drugs may be associated with low blood cell counts that can be severe and persistent.
  • Heart Problems: Certain monoclonal antibodies increase the risk of high blood pressure, congestive heart failure and heart attacks.
  • Lung Problems: Some monoclonal antibodies are associated with a higher risk of inflammatory lung disease.
  • Skin Problems: Sores and rashes on your skin can lead to serious infections in some cases. Serious sores can also occur on the tissue that lines your cheeks and gums (mucosa).
  • Bleeding: Monoclonal antibody drugs designed to stop cancer from forming new blood vessels have an increased risk of severe internal bleeding.

 

Will Monoclonal Antibody Therapy Help My Child with Cancer?

If you feel that your Child with Cancer may benefit from Monoclonal Antibody Therapy, discuss it with their oncologist.

Questions to ask your child’s doctor include:

  • Has my Child’s Tumour been tested to see if a Monoclonal Antibody Treatment might be of Benefit? (Simple tests on tumour samples can often tell if the currently available monoclonal antibody treatments might help your child’s specific cancer.)
  • Has the Monoclonal Antibody Drug shown a Clear Benefit? Ask your child’s doctor about evidence of the treatment’s effect in studies. Did it slow cancer growth? Did it result in reduced tumor sizes? Is this a first line of treatment or a treatment we try when others don’t work?
  • What are the Likely Side Effects of Monoclonal Antibody treatment? Together with your child’s doctor, you can determine whether the potential side effects of treatment are worth the likely benefit.
  • How much will Monoclonal Antibody Treatment Cost? Monoclonal antibody drugs can cost thousands for each treatment. Ask your care team to help you determine if the treatment is covered by your insurance.
  • Is Monoclonal Antibody Treatment available in a Clinical Trial? Clinical trials, which are studies of new treatments and new ways to use existing treatments, may be available to you. In a clinical trial, the cost of the monoclonal antibody drug may be paid for as a part of the study. Also, you may be able to try new monoclonal antibody drugs. Talk to your doctor about what clinical trials may be open to you.

 

Disclaimer:

Please note that the Little Fighters Cancer Trust shares information regarding various types of cancer treatments on this blog merely for informational use. LFCT does not endorse or promote any specific cancer treatments – we believe that the public should be informed but that the option is theirs to take as to what treatments are to be used. Always consult your medical practitioner prior to taking any other medication, natural or otherwise.